Low carbohydrate dieting plans are increasingly popular. Recent data from randomized clinical studies have shown that low carbohydrate diets have increased efficacy at 6 month time points as compared to low-fat diets. Despite the popularity and efficacy of low carbohydrate diets, little is known about the mechanisms through which they affect food intake and body weight. It has been suggested that transition from a carbohydrate to a lipid metabolism results in greater energy utilization but data from clinical studies suggest that reduced food intake accounts for the increased weight loss. We have conducted animal studies to begin to assess how low carbohydrate diets may affect food intake and body weight. Our preliminary data demonstrate that rats maintained on a low carbohydrate-high fat diet consume less food and gain less weight than rats on an ordinary high carbohydrate-high fat diet. Low carbohydrate diet rats also have increased sensitivity to the anorexigenic effects of a melanocortin agonist and decreased sensitivity to the orexigenic effects of a melanocortin antagonist. Furthermore, rats on a low carbohydrate diet do not show a rebound hyperphagia in response to food deprivation and patterns of hypothalamic gene expression in response to fasting are altered in a manner consistent with the lack of a compensatory feeding response. These data suggest potential mechanisms underlying the ability of low carbohydrate diets to produce weight loss without inducing "hunger". The proposed experiments will provide a more complete characterization of the consequences of consuming a low carbohydrate diet by 1) generalizing the findings to a diet composition similar to that consumed by individuals following Atkins-type diets, 2) assessing whether the response to melanocortins is specific or generalizes to other anorexigenic and orexigenic stimuli and 3) assessing how diet composition may differentially alter hypothalamic responses to the state of chronic food restriction that accompanies dieting.